ArticleProceedings of the National Academy of Sciences of the United States of America2021
Generating tumor-selective conditionally active biologic anti-CTLA4 antibodies via protein-associated chemical switches.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 44 citations in OpenAlex.
- Article
- The next generation of antibody-drug conjugates.Nature medicine · 2026Review
- The evolution of display technologies for antibody drug discovery.Trends in biotechnology · 2026Review
- Next-generation T cell engagers for cancer and autoimmune diseases.Frontiers in immunology · 2026Review
- Article
- Article
- T cell engagers: expanding horizons in oncology and beyond.British journal of cancer · 2025Review
- Fifty years of monoclonals: the past, present and future of antibody therapeutics.Nature reviews. Immunology · 2025Article
- Generation Using Phage-Display of pH-Dependent Antibodies Against the Tumor-Associated Antigen AXL.Antibodies (Basel, Switzerland) · 2025Article
- Preclinical development of mecbotamab vedotin (BA3011), a novel, AXL-specific conditional active biologic antibody-drug conjugate.Antibody therapeutics · 2025Article
- Nanobody-Targeted Conditional Antimicrobial Therapeutics.ACS nano · 2025Article
- Isoelectric point, net charge and amino acid analysis of experimentally validated therapeutic antibodies.In silico pharmacology · 2025Article
- Antibody-drug conjugates in cancer therapy: applications and future advances.Frontiers in immunology · 2025Review
- Antibody Drug Conjugates (ADCs): Shaping the Future of Precision Oncology.Anti-cancer agents in medicinal chemistry · 2025Review
- New immune cell engagers for cancer immunotherapy.Nature reviews. Immunology · 2024Review
- First Use of AXL Targeting in Metastatic, Refractory, Adenoid Cystic Carcinoma: A Case Report.JCO precision oncology · 2024Article
- Exploring the next generation of antibody-drug conjugates.Nature reviews. Clinical oncology · 2024Review
- Conditionally Active, pH-Sensitive Immunoregulatory Antibodies Targeting VISTA and CTLA-4 Lead an Emerging Class of Cancer Therapeutics.Antibodies (Basel, Switzerland) · 2023Review
- Immune checkpoint therapy for solid tumours: clinical dilemmas and future trends.Signal transduction and targeted therapy · 2023Review
- Immunotherapeutic Approaches in Ovarian Cancer.Current issues in molecular biology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Anticytotoxic T lymphocyte-associated protein 4 (CTLA4) antibodies have shown potent antitumor activity, but systemic immune activation leads to severe immune-related adverse events, limiting clinical usage. We developed novel, conditionally active biologic (CAB) anti-CTLA4 antibodies that are active only in the acidic tumor microenvironment. In healthy tissue, this binding is reversibly inhibited by a novel mechanism using physiological chemicals as protein-associated chemical switches (PaCS). No enzymes or potentially immunogenic covalent modifications to the antibody are required for activation in the tumor. The novel anti-CTLA4 antibodies show similar efficacy in animal models compared to an analog of a marketed anti-CTLA4 biologic, but have markedly reduced toxicity in nonhuman primates (in combination with an anti-PD1 checkpoint inhibitor), indicating a widened therapeutic index (TI). The PaCS encompass mechanisms that are applicable to a wide array of antibody formats (e.g., ADC, bispecifics) and antigens. Examples shown here include antibodies to EpCAM, Her2, Nectin4, CD73, and CD3. Existing antibodies can be engineered readily to be made sensitive to PaCS, and the inhibitory activity can be optimized for each antigen's varying expression level and tissue distribution. PaCS can modulate diverse physiological molecular interactions and are applicable to various pathologic conditions, enabling differential CAB antibody activities in normal versus disease microenvironments.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.